REVIEW
Omega-3 Fatty Acids for Cardioprotection

https://doi.org/10.4065/83.3.324Get rights and content

The most compelling evidence for the cardiovascular benefit provided by omega-3 fatty acids comes from 3 large controlled trials of 32,000 participants randomized to receive omega-3 fatty acid supplements containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or to act as controls. These trials showed reductions in cardiovascular events of 19% to 45%. These findings suggest that intake of omega-3 fatty acids, whether from dietary sources or fish oil supplements, should be increased, especially in those with or at risk for coronary artery disease. Patients should consume both DHA and EPA. The target DHA and EPA consumption levels are about 1 g/d for those with known coronary artery disease and at least 500 mg/d for those without disease. Patients with hypertriglyceridemia benefit from treatment with 3 to 4 g/d of DHA and EPA, a dosage that lowers triglyceride levels by 20% to 50%. Although 2 meals of oily fish per week can provide 400 to 500 mg/d of DHA and EPA, secondary prevention patients and those with hypertriglyceridemia must use fish oil supplements if they are to reach 1 g/d and 3 to 4 g/d of DHA and EPA, respectively. Combination therapy with omega-3 fatty acids and a statin is a safe and effective way to improve lipid levels and cardiovascular prognosis beyond the benefits provided by statin therapy alone. Blood DHA and EPA levels could one day be used to identify patients with deficient levels and to individualize therapeutic recommendations.

Section snippets

Background

During the past 3 decades, thousands of epidemiologic, observational, experimental, and randomized controlled studies have been published on the CV effects of omega-3 fatty acids. In the aggregate, these studies document clear CV protective effects.2 The 2 specific omega-3 fatty acids that have been associated with CV benefit and triglyceride lowering are those from fish oils, DHA and EPA. In contrast, ALA, which is found in abundance in flaxseed and to a lesser extent in walnuts and other tree

MECHANISMS OF ACTION

Omega-3 fatty acids appear to confer CV benefits largely through DHA and EPA enrichment of membrane phospholipids.9 Via this mechanism, omega-3 fatty acids can ultimately increase arrhythmic thresholds,10 reduce blood pressure,11, 12 improve arterial and endothelial function,13 reduce platelet aggregation,14 and favorably affect autonomic tone11, 15 (Table 2). In a meta-regression analysis of 22double-blind studies, Geleijnse et al16 reported that consumption of approximately 4.0 g/d of omega-3

OPTIMAL OMEGA-3 FATTY ACID MIX: DHA VS EPA

Both DHA and EPA are present in all oily fish, although at variable ratios (Table 3).27 Most commonly consumed fish, such as salmon, contain DHA and EPA in a ratio of approximately 2:1, whereas standard fish oil (usually derived from menhaden, an oily fish of the herring family) contains DHA and EPA in a 2:3 ratio. To a small extent, DHA can be retroconverted to EPA28; however, EPA supplementation does not increase tissue or blood levels of DHA.29 In vitro studies have shown both fatty acids to

ADVERSE EFFECTS

In prospective placebo-controlled trials, no adverse effects were observed to occur at a frequency of more than 5%, and no difference in frequency was noted between the placebo and omega-3 fatty acid groups.24, 40 The most commonly observed adverse effects are nausea, gastrointestinal upset, and a “fishy burp.” Steps to reduce burping and improve adherence include taking the omega-3 fatty acid at bedtime or with meals, keeping the fish oil capsules in the freezer, or using enteric-coated

PRIMARY AND SECONDARY PREVENTION OF CAD

To date, no randomized controlled trial has shown that omega-3 fatty acids reduce the risk of CV events and mortality in a primary prevention population. The evidence supporting a benefit in primary prevention comes instead from an observed 18% decrease in CV events in the 80% of patients in the JELIS trial without documented CAD (P=.13); this effect size was essentially the same as that observed in the secondary prevention cohort (19%, P<.05). In addition, prospective observational cohort

RECOMMENDATIONS FOR ADMINISTRATION

The correct dosage of any fish oil product can be calculated simply by adding up the amount of DHA and EPA per capsule and dividing this number into the target daily doses for triglyceride lowering or primary or secondary prevention. For example, the standard fish oil concentrate contains 120 mg of DHA and 180 mg of EPA per 1-g capsule. Thus, 1 to 2 capsules of standard over-the-counter fish oil per day (300-600 mg of DHA and EPA) would meet the recommendations for primary prevention; 3 to 4

CONCLUSION

Current data suggest that patients with known CAD should consume at least 1.0 g/d of long-chain omega-3 fatty acids; people without disease, at least 250 to 500 mg/d. Both DHA and EPA should be consumed. Regardless of statinuse, patients with hypertriglyceridemia benefit from treatment with 3.0 to 4.0 g/d of DHA and EPA.

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    Dr O'Keefe has received research grants from and is a consultant for CardioTabs. Dr Lavie has been a speaker and consultant for Reliant Pharmaceuticals. Dr Marchioli is a member of the steering committee of the Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial sponsored by Astra-Zeneca and Società Prodotti Antibiotici (SPA), a member of the steering committee of the Rischio & Prevenzione trial sponsored by SPA, and a speaker for SPA, Sigma-Tau, Solvay Pharmaceuticals, and Pronova BioPharma. Dr Harris is a consultant for and has received research grants from both Reliant Pharmaceuticals and Monsanto and is a speaker for the former.

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